Soft gelatin encapsulation of a solution or dispersion of a pharmaceutical agent in a liquid carrier offers many advantages over other dosage forms such as compressed, coated or uncoated solid tablets or bulk liquid preparations. Gelatin encapsulation of a solution or dispersion permits accurate delivery of a unit dose, an advantage which becomes especially important when relatively small amounts of the active ingredient must be delivered, as in the case of certain hormones. Such uniformity is more difficult to achieve via a tabletting process wherein solids must be uniformly mixed and compressed, or via incorporation of the total dose of active ingredient into a bulk liquid carrier which must be measured out prior to each oral administration.
Soft gelatin encapsulation provides a dosage form which is more readily accepted by patients, since the capsules are easy to swallow and need not be flavored in order to mask the unpleasant taste of the active principle. Soft gelatin capsules are also more easily transported by patients than bulk liquids, since only the required number of doses need be removed from the package.
Soft gelatin encapsulation further provides the potential to improve the bioavilability of pharmaceutical agents. Active ingredients are rapidly released in liquid form as soon as the gelatin shell ruptures. Complete disintegration and dissolution of the capsule are not necessary for the active ingredients to become available for absorption as in the case of tabletted compositions. Also, relatively insoluble active ingredients can be dispersed in a liquid carrier to provide faster absorption. In the case of an oral liquid preparation, a significant amount of the active ingredient is lost in the mouth or esophageal lining, prior to absorption into the blood.
Currently available antacid preparations are designed for the symptomatic relief of heartburn (pyrosis), sour stomach, indigestion, gas and the hyperacidity associated with peptic ulcer, gastritis, gastric hyperactivity and hiatal hernia. These preparations contain one or more basic magnesium, aluminum or calcium salts which act to neutralize stomach acid. For example, Maalox.RTM. Plus (W. H. Rorer, Inc., Ft. Washington, Pa.) is available as a liquid which is formulated to deliver 200 mg of magnesium hydroxide, 225 mg of aluminum hydroxide and 15 mg. of simethicone, a gas dispersing agent, per dose. The tablet form of this product is similar except that it contains 200 mg of aluminum hydroxide per dose. Tums.RTM. (Norcliff Thayer, Inc., Tuckahoe, NY) contains about 500 mg of calcium carbonate per tablet. Other commercially available antacid compositions contain varying amounts of magnesium silicate, magnesium carbonate, bismuth aluminate, magnesium oxide, dihydroxy aluminum sodium carbonate, magaldrate and similar basic salts.
The advantages which would be attained by delivering these salts as dispersions or solutions via soft gelatin encapsulation have been enumerated hereinabove. However, delivery of such formulations in this manner has not heretofore been possible due to the chemical destabilization of gelatin, i.e. of type A or B, in the presence of strongly alkaline salts, leading to the leaking or bleeding of the capsule contents at elevated pH. Further, the edible oils which have traditionally been used as carriers for pharmaceuticals in soft gelatin capsules effectively reduce the neutralizing capacity of the antacid components.
It is therefore an object of the present invention to provide liquid dispersions of basic salts which are suitable for, and compatable with, soft gelatin encapsulation.
It is another object of the present invention to provide dispersions of basic salts, e.g., calcium, magnesium and aluminum salts, which are adapted for oral, vaginal, rectal or buccal administration when contained within soft gelatin capsules.
It is another object of the present invention to provide dispersions of basic salts in carriers which do not adversely effect the neutralizing capacity of the basic salts.
Other objects, advantages and novel features of the present invention will be apparent to those of skill in the art from the following description and appended claims.